Medicinal compositions containing acetylsalicylic acid are well-known. It is also known that when acetylsalicylic acid is used in conjunction with other active ingredients the other ingredients can cause some instability in the acetylsalicylic acid resulting in the undesirable formation of salicylic acid or other reaction products. In order to prevent such instability, it is often necessary to physically separate the acetylsalicylic acid component from the other ingredients. This can be accomplished by using a layered composition, such as a layered tablet or press-coated tablet, or by coating the ingredients with a layer or film of suitable protective material.
When a nasal decongestant, such as phenylephrine hydrochloride, is used in conjunction with acetylsalicylic acid, the resulting combination causes considerable instability of the acetylsalicylic acid and reaction between the ingredients, such as formation of acetyl derivatives of phenylephrine, unless a coated or layered composition is employed. Such techniques can be complex and expensive. When an effervescent composition is desired, such techniques are either not feasible or they adversely affect effervescence or solution characteristics. It was known in the prior art that a stable mixture of acetylsalicylic acid and phenylephrine bitartrate could be employed without the requirements of layering or coating.
Recently it was proposed to replace phenylephrine with phenylpropanolamine as the nasal decongestant in admixture with acetylsalicylic acid. The only readily available salt of phenylpropanolamine was phenylpropanolamine hydrochloride. It is known that primary amines are more reactive than secondary amines. It was therefore reasonable to expect that salts of phenylpropanolamine (a primary amine) would be more reactive with and thus cause more instability of acetylsalicylic acid than salts of phenylephrine (a secondary amine). Phenylpropanolamine salts are also known to be pharmacologically less effective on a weight basis than phenylephrine salts. Therefore it requires more of the phenylpropanolamine salts to achieve the desired medicinal effect. The increased amounts of the more reactive phenylpropanolamine salts should reasonably cause more instability of acetylsalicylic acid that the corresponding salts of phenylephrine. The use of specific salts of phenylpropanolamine in direct contact with acetylsalicylic acid to provide a storage-stable composition is therefore an advance in the art.